TY - JOUR
T1 - All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma
AU - Dimopoulos, Meletios A.
AU - Grosicki, Sebastian
AU - Jędrzejczak, Wiesław W.
AU - Nahi, Hareth
AU - Gruber, Astrid
AU - Hansson, Markus
AU - Gupta, Neeraj
AU - Byrne, Catriona
AU - Labotka, Richard
AU - Teng, Zhaoyang
AU - Yang, Huyuan
AU - Grzasko, Norbert
AU - Kumar, Shaji
N1 - Funding Information:
The trial was designed by the lead and senior authors (M.A.D. and S.K.) in collaboration with the sponsor, Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. The sponsor funded collection, analysis, and interpretation of data. Manuscript preparation, approval, and the final decision to submit were led by the authors. FireKite, an Ashfield company, part of UDG Healthcare plc, provided writing support funded by the sponsor. All authors had full access to all study data, including the raw data, and agreed to be accountable for the accuracy and integrity of the data and analyses. The corresponding author had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2018
PY - 2019/1
Y1 - 2019/1
N2 - Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. Results: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61–87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1–29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). Conclusions: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. Trial registration number: NCT02046070.
AB - Background: Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance. Patients and methods: Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m2 of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction. Results: Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61–87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1–29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related). Conclusions: ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients. Trial registration number: NCT02046070.
KW - Elderly
KW - Multiple myeloma
KW - Newly diagnosed
KW - Oral therapy
KW - Transplant-ineligible
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UR - http://www.scopus.com/inward/citedby.url?scp=85056777478&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2018.09.011
DO - 10.1016/j.ejca.2018.09.011
M3 - Article
C2 - 30471652
AN - SCOPUS:85056777478
VL - 106
SP - 89
EP - 98
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -